Case management and plasma half-life in a case of brodifacoum poisoning.

Brodifacoum is a readily available, second-generation anticoagulant rodenticide (superwarfarin) that causes extended depletion of vitamin K1-dependent clotting factors. Brodifacoum ingestions are being reported with increasing frequency. For the first time, we compare plasma brodifacoum concentration to prothrombin levels over time in a case of brodifacoum poisoning. Brodifacoum was eliminated according to a two-compartment model, with an initial half-life of 0.75 days and a terminal half-life of 24.2 days. On admission, the brodifacoum level was 731 micrograms/L and the patient suffered severe urinary tract hemorrhage, requiring transfusion of blood products. Persistently increased prothrombin times necessitated treatment with phytonadione up to 80 mg/d for 4 months, until the brodifacoum level reached 10 micrograms/L. These data may help project the duration of phytonadione treatment required in future cases of brodifacoum poisoning. Superwarfarin exposure must be suspected in an otherwise unexplained vitamin K1-deficient coagulopathy.

Regional cerebral and neural lobe blood flow during insulin-induced hypoglycemia in unanesthetized rats.

The effects of hypoglycemia on regional cerebral blood flow (rCBF) were studied in awake restrained rats. The rats were divided into three groups consisting of a normoglycemic control group that received only saline, a hypoglycemic group A, which was given insulin 30 min before flow was measured, and a hypoglycemic group B, which was given insulin 90 and 30 min before flow was measured. Regional CBF was measured using 14C-iodoantipyrine. Mean plasma glucose was 8.76 mumol/ml in the control group, 2.63 mumol/ml in hypoglycemic group A, and 1.51 mumol/ml in hypoglycemic group B. Plasma epinephrine and norepinephrine concentrations increased to approximately 375% and 160%, respectively, of control values in hypoglycemic groups A and B. In the hypoglycemic group A, rCBF significantly increased in three brain regions. In the hypoglycemic group B, rCBF increased significantly in all brain regions measured, with the exception of the neural lobe, in which it decreased. The increase in rCBF ranged from 38% in the hypothalamus to 138% in the thalamus. Neural lobe blood flow significantly decreased by 31%. The neural lobe was the only brain region studied that is not protected by a blood-brain barrier. It may be sensitive to changes in the concentration of vasoactive agents in blood, such as epinephrine and norepinephrine.

Beta-receptor-mediated increase in cerebral blood flow during hypoglycemia.

We tested the hypothesis that beta-adrenergic receptor stimulation is involved with the increase in regional cerebral blood flow (rCBF) during hypoglycemia. Rats were surgically prepared with the use of halothane-nitrous oxide anesthesia. A plaster restraining cast was placed around the hindquarters, and anesthesia was discontinued. Hypoglycemia was produced by an intravenous injection of insulin (15 U/kg); normoglycemic control rats were given saline. Propranolol (1.5 mg/kg) was administered to some control and some hypoglycemic rats to block the beta-adrenergic receptors. Regional CBF was measured using 4-[N-methyl-14C]iodoantipyrine. Plasma glucose in the normoglycemic and hypoglycemic groups was approximately 6 and 1.4 mumol/ml, respectively. Regional CBF increased during hypoglycemia in rats that were not treated with propranolol. The increase varied from approximately 60 to 200% depending on the brain region. During hypoglycemia, propranolol abolished the increase in rCBF in the hypothalamus, cerebellum, and pyramidal tract. In other regions the increase in rCBF was only 33-65% of the increase in hypoglycemic rats that were not treated with propranolol. We conclude that beta-receptor stimulation plays a major role in the increase in rCBF during hypoglycemia.